Abstract
The incursion of B3.13 genotype H5N1 Clade 2.3.4.4b highly pathogenic avian influenza A virus (IAV) into US dairy cattle is unprecedented in the era of molecular diagnosis. This raises important questions around the likelihood of this avian-to-mammal spillover event occurring elsewhere. To address this, we challenged a wide array of bovine primary and continuous cells, including from mammary and respiratory tissue, with a panel of avian, human, swine and laboratory-adapted IAV strains and measured the kinetics of infectious virus replication. Across all virus strains, udder epithelial cells were the most susceptible, followed by lower respiratory tract cells. Upper respiratory tract cells and fibroblasts from most tissues tested were generally poor substrates for virus growth, while peripheral blood monocytes were also largely refractory. Virus strain had a strong influence on virus replication, varying (for instance) between undetectable and > 108 pfu/ml in highly susceptible udder cells. However, most IAV strains replicated well in udder cells. Importantly, viruses with high-growth phenotypes included human seasonal strains, low pathogenicity avian viruses and BSL2 reassortant viruses containing the PR8 glycoproteins and internal genes from recent UK Clade 2.3.4.4b H5N1 isolates. The set of BSL2 H5N1 reassortant viruses included a B3.13 cow isolate and although this generally grew the best of all strains tested, it was not significantly different from all other avian isolates. We conclude that the US bovine influenza outbreak does not simply reflect a unique adaptation of the B3.13 genotype virus; outbreaks of mastitis in dairy cattle should therefore include testing for IAV.
Co-Author(s)
Authors: Rute Maria Pinto1, Colin Sharp1, Maia Beeson1, Nunticha Pankaew1, Alex Moxom1, Stephen Meek1, Laura Tuck1, Wenfang Tan1, Inga Dry1, Hui Min Lee1, Jessica L. Quantrill2, Jiayun Yang3, Vihdi Dholakia4, Thomas P. Peacock3, Tom Burdon1, Xavier Donadeu1, Cristina Esteves1, Jayne Hope1, James Prendergast1, Sam Lycett1, Lu Lu1, Daniel Goldhill4, Wendy Barclay2, Munir Iqbal3, Eleanor Gaunt1, Paul Digard1.
Affiliations:
1The Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG
2Imperial College, South Kensington Campus, London SW7 2AZ
3The Pirbright Institute, Pirbright, Woking GU24 0NF
4Royal Veterinary College, Hawkshead Campus, North Mymms, Hertfordshire, AL9 7TA
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health